Governing nonconventional genetic experimentation

Abstract A large and highly heterogeneous group of individuals conducts genetic and genomic research outside of traditional corporate and academic settings. They can be an important source of innovation, but their activities largely take place beyond the purview of existing regulatory systems for promoting safe and ethical practices. Historically the gene-targeting technology available for non-traditional genomic research has been limited, and therefore these activities have attracted little regulatory attention. New technologies such as CRISPR/Cas9, however, give nonconventional experimenters more extensive gene editing abilities at an unprecedented level of accessibility. The affordability and accessibility of these powerful technologies are raising questions about whether the current largely laissez-faire governance approach is adequate. This article recommends steps to enhance self-governance, including establishing umbrella organizations to represent community interests, creating a community IRB modelled on the DIYBio Ask a Safety Expert Service, and adopting an ethical obligation to report rogue experiments.

amateur fossilist with numerous contributions to paleontology. 7 Modern nonconventional biology has been described as a return to Victorian and earlier models of scientific endeavor. 8 The members of the nonconventional biology community are highly diverse in terms of their background, interests, and values. Many nontraditional biologists rebel against the hierarchy and specialization of academic and corporate biology. 9 Some are employed in traditional biological institutions but pursue projects of personal interest in their free time. 10 Others are complete amateurs. As one commentator notes, 'it is experimenting on the cheap, usually without the benefit of a fancy university laboratory . . . . If you don't know enough biology to take part at first, you learn it along the way'. 11 Nonconventional biology is pursued individually and in teams, in individual homes and group labs, and no doubt on a moonlight basis in industry and academic laboratories. In the spirit of the 1996 Bermuda Agreement 12 and NIH policy on public access to genome sequencing data, 13 many nonconventional experimenters reject intellectual property rights and insist on an open-source approach. 14 Others actively seek to commercialize their discoveries. Some are public about their work, while others are secretive. 15 Nonconventional biology is financed in a number of ways, including personal funding, dues to labs, investors, and crowdfunding, such as Kickstarter, which for example raised $35,000 to start a community laboratory called BioCurious in Silicon Valley 16 and half a million dollars to create a company to sell bioluminescent plants. 17 Individuals and labs use reverse engineering and inexpensive, off-the-shelf parts to construct simplified and low-budget equipment. 18 As gene modification has become easier and more accessible with advances such as CRISPR ('clustered regularly interspaced short palindromic repeats'), a technology used to alter DNA sequences, 19 nonconventional biologists have begun to pursue gene editing. 20 CRISPR/Cas9 is relatively accurate, inexpensive, and easy to use. 21 Gene editing previously was practical only in a very limited number of cells and organisms, but CRISPR/Cas9 can be used to edit any cell or organism with a sequenced genome and with a way to introduce nucleic acids and/or proteins. As the former principal investigator of the Synthetic Biology Project at the Woodrow Wilson Center stated in 2016, 'the equipment and reagents that are needed to use CRISPR-Cas9 are already readily available'. This is still true. 22 Anyone can purchase a genome editing kit for as little as $200 and start tinkering with the delicate instructions of life. 23 A recent report projected that the market for NGE supplies would reach over $52 million by 2027. 24 The more basic NGE CRISPR experiments include creating a streptomycinresistant strand of Escherichia coli, 25 inserting a jellyfish gene into yeast to make glowing beer, and genetically modifying frogs to increase in size and weight. 26 However, many amateurs are becoming increasingly sophisticated in their projects. Reagent introduction can be difficult for some target cells and organisms, but easier for others (eg direct injection into muscle, inhalation of aerosolized particles, microinjection of fish or amphibian eggs). 27 Experimenters can select target organisms from the increasing number of organisms with sequenced genomes and obtain reagents and viral vectors from commercial suppliers, in some cases, as discussed below, 28 by circumventing sales restrictions. 29 One nontraditional biologist is described as 'cutting, pasting and stirring genes, as simply as mixing a vodka tonic, . . . after which he slides his new hybrid creations, living in petri dishes, onto a refrigerator shelf next Nonconventional genetic experimentation (NGE) gained public attention in the early 2000s. An international competition for high school and college students called the 'International Genetically Engineered Machine' (iGEM) was founded in 2003 at MIT 'to show that it does not take a doctoral degree to design a biotechnology product'. 38 In a recent iGEM competition, 20 teams used CRISPR. 39 An announcement in 2008 of the creation of a synthetic genome that did not exist naturally 40 increased interest in genetic engineering, including NGE. A year later, Mac Cowell and Jason Bobe started 'DIYBio.org' as a shared space for NGE experimenters. 41 Local, community, and regional labs were established, including BioCurious in Silicon Valley and GenSpace in New York. 42 Equipment costs declined, and NGE experimenters reverse-engineered their own equipment. 43 In 2015, an international effort called the Open Insulin Project debuted with the goal of using NGE to genetically engineer yeast and E. coli in order to produce insulin, which would be sold at a fraction of the cost of commercially manufactured products. 44 In 2017, Josiah Zayner, who started a company called The Odin that sells NGE materials and equipment, including CRISPR kits, livestreamed injecting CRISPR-edited DNA in a vain effort to grow muscle by knocking out his myostatin gene. 45  A major potential benefit of NGE, as with amateur science in the past, is innovation. 47 In the case of computers, for example, Steve Jobs and Bill Gates did early work in their garages, 48 and the first Apple was unveiled at a local electronics hobby club. 49 NGE innovation can be fostered by experimenters having greater experimental freedom outside of traditional settings and more cross-disciplinary collaboration. 50 NGE also can produce a broader pool of science talent 51 and enhance science education. 52 NGE also could be employed to improve access to certain types of health care. As mentioned earlier, 53 the Open Insulin Project, which began in 2015 in a community lab in Oakland, aims to establish a network of community-based production sites to manufacture insulin and sell it to diabetics for $7 a vial 54 rather than the current $175 to $300 cost for commercially manufactured products. 55 As one set of commentators observes: Biohacker spaces hold great potential for promoting innovation. Numerous innovative projects have emerged from these spaces. For example, biohackers have developed cheaper tools and equipment. They are also working to develop low-cost medicines for conditions such as diabetes . . . . On an economic level, biohacker spaces facilitate entrepreneurship by providing tools, training, and resources to help people prototype their biotechnology-based ideas. Biohacker spaces also help advance scientific research.
There are many examples of ambitious projects that have derived from these spaces such as vegan cheese protein, genetically engineered bacteria that can sense arsenic, as well as robots that can automate lab work. 56 The commentators note that NGE innovation can take place despite the conventional intellectual property protections that characterize traditional biomedical research: Biohacker spaces demonstrate that innovation can arise outside of the formal IP system in a way that embraces open science and inclusivity . . . . A number of projects have emerged from biohacker spaces in the shadow of the formal IP system. For example, a group of biohackers developed Open Trons, an open source lab robot to automate lab work. The project originated from Genspace and raised well over $100,000 on Kickstarter, meeting 125% of its fundraising goal. Besides being a commercially successful campaign, the project also achieves other inclusive outcomes: it enhances understanding of lab automation through its open source technology and its low price compared to other lab automation robots enables access to this technology in labs that cannot afford the more expensive robots. 57 Yet NGE creates safety risks. After 9/11, nonconventional biology raised concerns about bioterrorism, and the FBI placed its activities under surveillance. 58 In 2004 and 2008, agents raided basement laboratories on suspicion of possession of dangerous chemicals. 59 In 2006, the agency established the Weapons of Mass Destruction Directorate (WMDD), which continues to monitor nonconventional biological experimentation, and created within the Directorate the Synthetic Biology Outreach Program (SBOP) under Supervisory Special Agent Edward You. 60 Since 2009, the FBI has sent observers to NGE meetings, conferences, and labs, 61 including the infamous hacker convention, DefCon. 62 Jason Bobe, co-founder of DIYBio, quipped in 2010 that '30% [of people on DIYBio e-mail] are spammers and the other 70% are law-enforcement officials keeping tabs on the community'. 63 While its early response to nonconventional biology was aggressive, the FBI's more recent approach is one of engagement and cooperation. 64 In some cases, community labs keep agents apprised of their events and experiments. 65 The FBI has organized annual NGE conferences where it fosters safety training, and the bureau has even 57  sponsored iGEM, prompting some jokingly to observe that 'DIYbio would not be where it is today without the FBI's support'. 66 A source of concern about NGE besides bioterrorism is the potential for experimenters to pose purposeful or accidental biosecurity threats by creating new or modified organisms that could harm human health or the environment. In an article in the New Yorker, for example, a science writer who admits having 'almost no experience in genetics and [having] not done hands-on lab work since high school' described how she was able to modify bacteria to make them drug-resistant using a 'bacterial CRISPR and fluorescent yeast combo kit' she purchased for $209 from Zayner's California company, The Odin, which sells genetic engineering kits to NGE experimenters: [B]y following the instructions that came in the box from the Odin, in the course of a weekend I was able to create a novel organism. First I grew a colony of E. coli in one of the petri dishes. Then I doused it with the various proteins and bits of designer DNA I'd stored in the freezer. The process swapped out one 'letter' of the bacteria's genome, replacing an ' A' (adenine) with a 'C' (cytosine). Thanks to this emendation, my new and improved E. coli could, in effect, thumb its nose at streptomycin, a powerful antibiotic. 67 Although in this particular case, streptomycin-resistant E. coli are prevalent and common in meat products in the United States due to agricultural use of streptomycin, 68 modified bacteria could cause infections that were difficult or impossible to treat with available antibiotics. If released intentionally, such infectious agents could be a potent weapon of mass destruction.
Another worrisome possibility is that NGE experimenters could intentionally create and release modified organisms with 'gene drives', which enable genetic modifications to spread through wild populations much faster than normal and potentially replace natural genomes. 69  The genetic material that encodes for those three elements gets inserted into an animal's DNA, in place of the naturally occurring gene you want to replace in both chromosomes. The power of the gene drive is that it disrupts the laws of heredity . . . . In normal heredity, there is a 50% chance that any particular gene will be passed from parent to offspring. Gene drive technology turns a 50% chance into a nearly 100% guarantee. When an animal carrying the gene drive package mates with an animal that does not, their offspring gets one copy of DNA from either parent: a natural version and a gene drive version. When the sperm meets the egg and the chromosomes from the different parents line up for the first time, CRISPR in the gene drive DNA is activated. It recognizes the copy of the natural gene in the opposite chromosome, and directs the DNAcutting Cas9 enzyme to cut out the natural copy before embryonic development begins. Once the natural gene is damaged, the cell's special repair machinery is triggered. The repair machinery restores the missing DNA, but it uses the unbroken chromosome, which is the one carrying the gene drive, as its template. So when the repair is finished, both chromosomes carry a copy of the gene drive. From that point on, two copies of the gene drive will be in every cell and the animal will pass the gene drive on to the next generation. And so the process continues. Every time the drive is passed on, CRISPR cuts the natural version of the gene, cell repair machinery intervenes and one copy of the gene drive becomes two. In just a few generations the new gene becomes ubiquitous in the population, sometimes totally replacing the naturally occurring gene.' the spread of malaria by mosquitoes and other insect-borne pathogens. 70 An effective gene drive would introduce genetic modifications into the target insect population at a highly accelerated rate to eliminate or reduce the population or to modify the population so that it could not transmit the disease pathogen. 71 Gene drives also could be used to combat agricultural pests and non-native species that threatened native plants and animals. 72 But gene drives raise concerns about unintended consequences, such as off-target effects or the modified genes being transmitted to other closely related species. 73 NGE also poses risks to subjects. These can be animals, humans, or the experimenters themselves, such as in the case of Josiah Zayner, as noted above. In another livestream in 2018, a biohacker injected himself with a treatment for genital herpes. 74 If the subjects of NGE experiments were individuals other than the experimenter, questions might arise about whether they gave appropriate informed consent, and whether they were ill and seeking an experimental intervention hoping that it would be more effective or less expensive than conventional treatments 75 In an NGE conference in Las Vegas in August 2019, for example, Zayner suggested that, to sidestep what he sees as accessibility and regulatory hurdles in conventional medicine, NGE experimenters who are collaborating with patients might consider working outside US borders in countries with less government oversight. 76 Finally, despite its potential to increase accessibility to expensive therapeutics, NGE could have disruptive effects on the innovation models of traditional pharmaceutical and biotechnology industries. Under American patent law, an invention can be patented only if it is novel and nonobvious, which would be defeated if an NGE experimenter had created a sufficiently similar product or process and it was 'described [it] in a printed publication, or in public use, on sale, or otherwise known to the public before' the traditional biology innovator filed a patent application. 77 As noted earlier, some NGE experimenters explicitly aim to thwart intellectual property rights and pursue an opensource approach to their discoveries, such as in the case of the biohackers who claimed to have made a copy of one of the world's most expensive gene therapies, Glybera In addition to the FBI, the FDA's regulatory authority covers many aspects of NGE. To the extent that NGE experimenters are seeking to develop therapeutic interventions, such as Zayner's myostatin treatment, the agency claims that they are producing and testing gene therapy products that come within the definition of 'biologics' in the Federal Food, Drug, and Cosmetic Act. 79 In 2017, the FDA issued a statement entitled 'Information About Self-Administration of Gene Therapy' which asserted that it is illegal to sell 'gene therapy products intended for self-administration and "do it yourself " kits to produce gene therapies for self-administration' without an approved IND or Biologics License Application. 80 Some commentators maintain that the FDA has broad jurisdiction over NGE because much of its materials and equipment are 'drugs'. 81 The ability of the FDA to regulate NGE, however, is substantially limited. For example, the agency lacks authority over interventions that experimenters make without using products or components in interstate commerce, as well as over instructions for experimentation that are not tied to a product or producer. 82 Furthermore, the FDA's broad authority to inspect commercial experimenters and manufacturers would not extend to inspecting NGE experimenters in their homes, which might require a warrant. 83 Even if the agency wanted to regulate NGE, the resources needed to do so effectively would be prohibitive. As Evans states, 'The staffing and budgets required to enforce regulations against thousands of tiny at-home operations could make regulation, as we knew it in the twentieth century, unworkable, especially if [NGE] grows more widespread than it is today'. 84 Finally, while some NGE experimenters are eager to share their work with others on social media and at conferences, others are highly covert, and therefore may remain under the FDA's radar. 85 In the exercise of discretion, therefore, the FDA so far has not pursued any enforcement activities against specific NGE individuals or activities. 86 The Environmental Protection Agency regulates microbial pesticides under the Federal Insecticide Fungicide and Rodenticide Act, as well as other recombinant DNA microbes and algae 'intended for general commercial and environmental applications' under the Toxic Substances Control Act, 87 but 'the reach of the law is limited to commercial or commercial research and development activities [and] it is unclear that 79 Information About Self-Administration of Gene Therapy, U.S. Food and Drug Administration (Nov. 11, 2017), https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/information-a bout-self-administration-gene-therapy. 80 89 In 1992 and again in 2017, the federal government revised the Coordinated Framework for the Regulation of Biotechnology Products, 90 but the Framework gives federal agencies no new regulatory powers over biotechnology, and the revisions did not address drugs, biologics, or medical devices derived through biotechnology. 91 NIH oversight is limited to research that is federally funded or conducted at academic institutions that receive federal funding. Intentional or reckless releases of engineered bioterror agents would be crimes, 92 and humans whose health or property were harmed by such a release or by other types of unethical experimentation might seek to recover damages in civil suits 93 ; but it may not be possible to hold the experimenters accountable because their identities may not be known, they may not be subject to US legal jurisdiction (for example, they may not be extraditable from a foreign country), or they may not have the assets to pay court-awarded damages. 94 The only state law specifically addressing NGE was passed in California in 2019 as a response to Josiah Zayner's 2017 public attempt to alter his myostatin gene. 95 The bill, which was introduced by Republican state senator Ling Ling Chang and passed unanimously by the state legislature, prohibits the sale of 'gene therapy kits', defined as 'a collection of materials for the purpose of facilitating gene therapy experiments', unless the package bears a warning label stating that the kit 'is not for self-administration'. 96 According to an article in the MIT Technology Review, there are no products currently for sale that fit the definition of the kits in the law. 97

III.B. Non-Governmental Regulation
Some efforts at non-governmental regulation have been made by the biotech industry. In response to calls by the Department of Health and Human Services 98  Department of Homeland Security 99 for commercial suppliers of potentially dangerous reagents and synthetic genetic material to screen customers, members of the International Gene Synthesis Consortium and others voluntarily have agreed to ship reagents only to 'valid business locations', and to decline to ship to home addresses and post office boxes. 100 However, NGE experimenters report that these suppliers do not verify whether their products are actually being shipped to a commercial establishment, as opposed to an experimenter's personal address with a fictitious company name. 101 The NGE community itself has taken a considerable number of self-regulatory steps. One of the reasons for the creation of DIYBio.org in 2009, according to co-founder Jason Bobe, was 'for amateur biotechnologists to have a focal point . . . to think through issues that are beyond the scope of any one amateur, such as safety and regulations for individuals working outside of traditional settings'. 102 In 2011, a North American DIYbio Congress adopted a code of ethics, described in 2013 as 'to date perhaps the most explicit example of the community's wish to find a "soft" yet binding way to create a common set of values and principles for its members'. 103 A companion code was adopted in 2011 in Europe. 104 However, the safety directive in both the North American and European codes merely states: ' Adopt safe practices'. 105 In 2013, DIYBio launched an ' Ask a Biosafety Expert' (ABE) service staffed by volunteers that responded to questions from nontraditional biologists. 106 The service was discontinued due to the cost of liability insurance. 107 In 2017, members of the NGE community convened the first Global Community Bio Summit, which has been followed by four others. The third meeting, held in 2019, adopted a 'Community Ethics Document 1.0' with 12 principles in the form of questions which organizers hoped could serve as an ethics 'decision-making template' for community labs and NGE researchers 108 One, called 'Transparency,' asked: 'How do we stay honest and open about our failures? How can we acknowledge ethical conflicts?' Another principle, 'Safety', asked: 'How do we embrace safe practices within unconventional contexts? How can we protect each other and create resources for communities to experiment safely?' Finally, the principle of ' Accountability' asked 'How will we hold each other accountable? How do we make ourselves accountable to people outside this community?' 109 At the fourth Global Community Bio Summit in 2020, a group of community biosafety leaders launched a 260-page 'Community Biology Biosafety Handbook', described as 'an open manual that offers biosafety protocols, practices, and recommendations aimed specifically for the community biology movement'. 110 As an open manual, the format of the Handbook is a Google Doc: The handbook is designed as a living document that can be updated and expanded by the community. Because both biotechnology and the Community Biology movement are rapidly evolving, the information here will need to be updated periodically. Also, given the variety of labs, the diverse local and national laws and regulations around labs, and the variety of interests among lab members, there will always be more that can be covered. 111 The Handbook is focused on community labs. For example, it recommends that labs have 'at least one point person who screens projects for safety (eg biological, physical, and chemical) and a committee of people to assist that point person in making decisions about safety and security'. 112 The Handbook also recommends that labs 'recruit expert advisors outside of the organization who you can consult when the safety of a project is in question or is beyond the expertise of the internal safety point person or committee. These consultants can be safety officers at universities, safety committees at other community biology labs, or colleagues in biotech or university labs who might be an expert in a field related to a proposed project'. 113 Although the Handbook is focused on community labs, its preamble states that 'it includes advice for . . . labs within homes and garages'. 114 In addition to recommendations for how community labs can be run safely, it contains general information about mitigating safety risks associated with NGE, including risks to the environment and other organisms, including humans, from genetically engineering organisms. 115 However, the Handbook currently does not provide specific safety recommendations for using newer gene editing techniques such as CRISPR, stating that 'the biosafety requirements related to new methods of modifying the genome are still not entirely clear', and that 'no particular guidelines for working with these methods have been published by the NIH or other regulatory agencies'. 116 The Biosafety Handbook also addresses the problem of desperate patients seeking cheaper or more effective treatments. 117 After noting the emotional challenges and potential for legal risk and adverse publicity, the Handbook advises community labs to either ignore the inquiries, decline with compassion, or refer the inquirer to 'professional resources'. 118 Community labs promote safe experimentation in a number of other ways. Most of them restrict their members to Biosafety Level 1 experiments, 119 which do not present significant health risks to humans or the environment. 120 (However, at least one community lab, Counterculture Lab in Berkeley, California, allows Biosafety Level 2 experiments, 121 which can pose moderate hazards. 122 ) Community labs also typically require members to agree to adhere to safety codes of conduct. BioCurious, in Sunnyvale, California, for example, has the following Code of Conduct: All protocols for workshops, and projects, or activities need to be run through the BioCurious Safety Group. BioCurious must be informed of all reagents which will be entering the lab, ahead of time and the type of laboratory support required. This ensures safety for all. Biosafety level 1 guidelines will be the limiting factor for projects, unless specifically noted otherwise. Only procedures which are approved and can be supported by BioCurious personnel and facilities will take place. No human sampling or injecting of substances are allowed.
Genetically modified materials need to stay in the lab in which they were developed 123 .
Labs also usually require members to run their proposed experiments past a lab safety committee. 124 During the height of the early months of the COVID-19 pandemic, a virtual community lab that hosted participants from around the globe, the Just One Giant Lab ( JOGL) platform, became a hub for NGE activity related to open source work on coronavirus research, which raised the usual biosafety concerns. During this time, the JOGL community developed a biosafety advisory board and a unique set of biosafety guidelines as well as a Code of Conduct. 125 Finally, the NGE community conducts robust conversations on social media platforms, such as the DIYbio.org Google Group, the Biohacking and Genetic Design Network, DIYBio, SyntechBio Biohacking Network, and Biohackers (GLOBAL), which are all on Facebook. 126 These conversations include discussions about safety issues, such as inquiries and responses in 2020 about epigenetic gene therapy for rejuvenation 127 and the safety of using lysed E. coli as an adjuvant in vaccine development. 128

IV. OTHER REGULATORY OPTIONS
If necessary, additional forms of regulation could be imposed on NGE. One option is greater governmental control. Certain other activities with robust independent research communities provide an analogy.
In the case of amateur or 'sport' rocketry, for example, the Federal Aviation Administration regulates the maximum height that sport rockets may reach. 129 The Bureau of Alcohol, Tobacco and Firearms (BATF) requires permits for 'toy' rockets that are sold in interstate commerce, only grants permits to US citizens over the age of 18 who pass a background check, and limits propellants to 62.5 g. The US Department of Transportation regulates propellants as explosives under rules harmonized with the BATF. Legal violations carry both civil and criminal penalties.
In 2015, Congress passed a law governing both commercial and recreational drones and requires the two uses to be kept separate. 130 With the passage of the National Defense Authorization Act of 2017, the FAA began requiring registration (for a $5 fee) if the weight of the recreational drone exceeds 0.55 pounds, prohibits weights over 55 pounds unless specially certified, and restricts operation near airports. 131 Finally, federal law, enforced by the BATF, prohibits the sale of home brewing products and limits home production to 100 gallons per year per adult, with a maximum of 200 gallons per household, and some state laws restrict alcoholic content and shipment. Violations carry criminal penalties. 132 In the case of NGE, the FBI could step up its monitoring of NGE experimentation, keeping a more wary eye out for questionable activities and even placing informants in NGE community labs and events. The FDA could increase regulation of NGE, and Congress could more clearly articulate the FDA's authority to cover experimentation without commercial ambitions. 133 At the extreme, states and the federal government could seek to make NGE illegal. German law, for example, prohibits gene editing outside of licensed laboratories. 134 However, such draconian regulation might run afoul of Constitutional protection of free speech and scientific inquiry. 135 It also would create incredible burdens for academic and industry researchers who might seek to collaborate with NGE projects and curtail the potential social and scientific advancements the community might offer.
Another option for NGE is indirect government regulation. For example, the government could make it illegal for suppliers to ship reagents to unapproved purchasers. As noted earlier, some suppliers voluntarily sell reagents only to 'valid business locations', but experimenters still get the reagents by using fictitious business addresses. 136 In response, the government could require suppliers to verify more effectively the business address of the purchaser, inspect suppliers to ensure compliance, and penalize willful or negligent noncompliance.
An alternative to focusing reagent shipment restrictions on purchasers' business addresses would be to require reagent purchasers to be licensed. 137 Licenses could be issued by the government, or by an organization within the NGE community, such as a consortium of community labs. Precedent for the latter is found in the licensing scheme for amateur ('ham') radio, which is overseen by the Federal Communications Commission, but established and operated by the ham radio community itself through organizations such as the Amateur Radio Relay League (ARRL). Volunteers who are themselves licensed administer written ham radio licensing examinations, using questions prepared by volunteer-examiner coordinators in 13 regions that have coordinator agreements with the FCC. Potential public benefits such as facilitating emergency communication during natural disasters were identified, but also concerns about interference between amateurs and government or commercial channels. In response, Congress passed the Radio Act of 1912, which required amateur operators to be licensed and restricted them to a single wavelength of 200 m. This caused a drop-off in ham radio use, leading operators in 1914 to organize the American Radio Relay League (ARRL) to represent and lobby for their interests. The value of ham radio was recognized during the First World War, but the practice was conducted under military supervision. The Navy wanted to continue to control the practice after the war, but the ARRL opposed this and independent amateur radio returned. In 1927, the federal Radio Act gave authority over amateurs to the Federal Communications Commission. In the 1950s, the FCC created different classes of amateur licenses, but there were few differences between what the classes could do, so in the 1960s, the FCC adopted 'incentive licensing', which gave higher classes greater access to wavelengths. Localities imposed restrictions and zoning rules to control the location of ham radio towers, which led to litigation. The FCC has issued a preemptive ruling stating that local governments must reasonably accommodate amateur operations, but they may still zone for height, safety, and aesthetics concerns. Given the risks posed by NGE noted earlier, some commentators see a need for greater oversight. Landrain and colleagues, for example, state that 'DIYbio still needs to find an active and, above all, binding way to deal with regulatory and safety issues'. 139 Arthur Caplan and colleagues suggest creating 'an international clearinghouse with which genetic sequence producers and sellers must register [and that] . . . would require all registered companies to monitor their orders and make sure that those who order biological material that could be misused have appropriate credentials, containment facilities, and training'. 140 Wexler et al. highlight the importance of 'community-developed standards and attention to sites of ethical gatekeeping' as well as the imperative that the community 'fosters partnerships between outside experts and DIY biologists' to help develop community standards for biosafety. 141 In 2010, the Presidential Commission for the Study of Bioethical Issues expressed the concern that 'the DIY research communities and other private researchers are exercising such freedom but without the institutional norms and procedures designed to assure responsibility . . . '. 142 Nevertheless, the current regulatory framework, with its focus on self-regulation, appears to be adequate at this time. Marketed results from NGE experiments seem to be effectively regulated by government agencies such as the FDA and the EPA. The FBI successfully monitors NGE activities for bioterrorism. Community labs seem to be doing a satisfactory job of overseeing experiments by their members, and there are no reports of dangerous lapses. Although there have been some troubling reports of self-experimentation outside of community labs, they do not appear to have produced serious harm, and if the self-experimenters are competent adults who are not engaging in interstate commerce, and are not violating any laws. 143 Finally, work with infectious agents that have the potential for harm to humans, animals, plants, or the environment requires a level of sophistication not present in most home laboratory settings.
Furthermore, continuing to rely primarily on NBE self-governance yields important benefits. It affords experimental freedom, improving the prospect of socially and scientifically valuable discoveries. It allows for open and friendly collaboration with industry and academia, as the trend toward open science grows in popularity. It is consistent with the anti-establishment values of many NGE experimenters. Most importantly, it reduces the likelihood that experimenters would be driven underground, where they conducted risky experiments with less community awareness and potential oversight.
There is no way to be certain about the future, however. Overly ambitious experimenters could deliberately or inadvertently ignore community safety codes. Entrepreneurs could market more advanced equipment that enabled more elaborate experimentation. More powerful new gene editing techniques could emerge. It must be stressed that serious safety and ethical concerns would arise not only if NGE gene editing experiments were successful, but also if the apparent ease and relatively low 139  cost of these techniques led to overly ambitious experiments that failed, causing harm to the environment and to human and nonhuman subjects.
Hence, the NGE community should consider forestalling greater external regulation by taking steps to enhance self-governance.

VI.A. NGE Umbrella Organization
The NGE community could establish one or more umbrella organizations to accomplish certain community-wide tasks discussed below. One model is DIYBio. Founded in 2009, DIYBio created community-wide Facebook groups, blogs, and an ' Ask a Biosafety Expert' (ABE) Service, held meetings, and promulgated a Code of Ethics. 144 Although the organization still has a website, 145 it essentially ceased operations in 2018. 146 Other potential successor organizations are the Global Community Bio Summit or JOGL, described above. 147 Another possibility is for community labs to establish an umbrella organization.
One purpose for such an NGE organization would be to adopt ethical and safety recommendations for NGE experiments. As described above, the Global Community Bio Summit is pursuing this through its ongoing Community Biology Biosafety Handbook project. 148 An additional step would be for the Bio Summit to invite individuals outside of the community, such as research, legal, and bioethics experts and government regulators, to review and comment on the recommendations, similar to what was done with the Human Augmentation Institute Draft Code of Ethics. 149 Another function of community-wide organizations could be to represent the interests of the NGE community before the FDA and other federal agencies, Congress, and state legislatures and administrative agencies. Hobbies subject to external oversight such as ham radio, sport rocketry, drones, and home brewing all have such organizations. Ham radio operators are represented by the National Association for Amateur Radio, which goes by the initials ' ARRL' that stand for the Amateur Radio Relay League. 150 Amateur or 'sport rocketry' enthusiasts have two groups, the National Association of Rocketry and the Tripoli Rocketry Association, which, in addition to promulgating safety codes 151 and lobbying legislatures, bring lawsuits against overzealous government regulators and offer liability insurance to their members. 152 These two organizations also belong to the National Fire Protection Association, a non-governmental organization that adopts model fire safety codes for rocket launches that are adopted in turn as is or in modified form by state and local governments. 153 Recreational drone operators belong to a number of organizations including the Academy of Model Aeronautics and the Drone User Group. 154 Home brewers, in an interesting twist, are represented by the American Home Brewers Association, a division of the commercial Brewers Association. 155

VI.B. NGE Community Review Board
Community labs, as noted earlier, typically have safety rules and individuals or committees to provide safety training and advice to members. 156 Training and advice also is available at NGE meetings and competitions, such as iGEM's Safety Hub. 157 Since the demise of DIYBio's Ask a Safety Expert Service, however, no consultative resources are available for independent experimenters working on their own 158 outside the JOGL platform, which still offers a place for members to ask questions on Slack. Therefore, one important self-regulatory step would be to re-establish such a resource.
One option is 'community review,' whereby experimenters would present their proposed projects to the NGE community at large, such as via a blogpost, and receive comments from whatever members who chose to respond. 159 This could be a valuable resource, but its usefulness would depend on which members participated and how expert they were in the issues presented. Moreover, projects posted on the web are likely to either be completely public or widely viewed by members of the community, which could deter experimenters who preferred to keep their projects confidential.
A more formally organized community review board (CRB) modeled on the DIYBio's Ask a Safety Expert Service would be an additional valuable resource. It would resemble the institutional review boards (IRBs) that are required by law to review and approve human experiments that are funded by the federal government or that research biomedical products needing government approval before they can be marketed. Submission of projects for review by the CRB, however, would be voluntary.
The idea of an IRB-type entity for 'citizen scientists' appears to have been broached first in a Scientific American Blog by Jessica Richman and Zachary Apte in 2013. 160 Calling it a 'mini-IRB,' they described it as: A publicly available IRB for citizen scientists, which would ensure that the creators had undergone ethics training, had considered how their project would affect the participants, that was available at a fairly low (and fixed) cost and could be achieved within a finite amount of time. This 'mini-IRB' would not be a full review, but would ensure that it was clear who was responsible for the project, that they had done their due diligence, and that participants were informed of the risks and benefits. 161 The third Global Community Bio Summit discussed creating what they called a 'Biohacker IRB'. 162 Members of JOGL have also indicated interest in establishing an NGE IRB. 163 Establishing a CRB faces several challenges. First, a process would be needed to identify the expert members. Like the experts who served on the Ask a Safety Expert Service, they would be volunteers. They could be selected by the community organization described earlier or by individual or groups of community labs, or they could be nominated or self-nominated. They could be encouraged to be Registered Biosafety Professionals and Certified Biological Safety Professionals with the American Biological Safety Association like the members of the Ask a Safety Expert Service, 164 or these or similar credentials could be required. To promote community acceptance, members of the community could be invited to vote on the candidates. They could serve without compensation, or they could be given honoraria. Either way, like the members of the Ask a Safety Expert Service, they should be covered by CRB liability insurance in case someone was injured in an experiment that they had reviewed. 165 Operating a CRB requires funding. As noted earlier, DIYBio's Ask a Safety Expert Service was discontinued due to the cost of liability insurance. CRB members might be given honoraria, and the CRB needs administrative support to manage its operations. The NGE community should consider the recommendation made by Jessica Richman and Zachary Apte in their 2013 blog mentioned above that funds be obtained from the NIH or the National Science Foundation or from crowdfunding platforms such as Microryza or Medstartr. 166 As stated above, consultations with the CAB would be voluntary. Voluntary consultation could be incentivized, however. The CRB could arrange for liability insurance for experimenters who submitted their projects for CRB review; similar insurance is offered to members of the National Association of Rocketry, 167 the Academy of